Background: Elvitegravir is an investigational once-daily integrase inhibitor with a long half life, and robust PK with trough levels of over 10-fold in excess of IC95. Methods: Adults with plasma HIV-1 RNA ≥1,000 copies/mL, and either resistance or six months experience to > 2 classes of antiretroviral drugs were randomized to receive blinded elvitegravir (EVG) 150 mg QD (85 mg if with atazanavir/lopinavir) or raltegravir (RAL) 400mg BID, in addition to a background regimen (BR) of a fully active ritonavir-boosted protease inhibitor and a second agent (investigator choice). The primary endpoint was the proportion of subjects achieving and maintaining HIV RNA < 50 copies/mL through Week 48 by TLOVR algorithm, with a non-inferiority threshold set at -10% (EVG-RAL). Results: 702 patients were included in the ITT analysis, mean age was 45 years; 82% were male; 45% had CD4 cell counts ≤200; 26% had HIV RNA >100,000 copies/mL; and 63% had baseline resistance to two or more ARV classes (primary PI 33%, NRTI 72%, and NNRTI 61%). The most common BR combination was Darunavir , Ritonavir and Tenofovir DF (24%).

Key 48 Week Results

Elvitegravir

Raltegravir

Elvitegravir vs. Raltegravir

HIV RNA < 50 copies/mL(TLOVR)
Responder, n (%)

207/351 (59%)

203/351 (58%)

95% CI, -6.0% to 8.2%, * p= 0.001 for non inferiority

Increase in CD4 cells/mm3, mean

138

147

Development of Integrase Resistance

16/62 (26%)

15/76 (20%)

Discontinuations due to Adverse Events, n (%)

9/354 (3%)

15/358 (4%)

[table 1]

Adverse events (AE) and laboratory abnormalities were similar.Conclusion: This study demonstrated that once daily EVG was non-inferior to twice daily RAL in treatment-experienced HIV-1 infected subjects.